Mavorixafor in WHIM Syndrome

  • WHIM syndrome is a rare and often difficult-to-diagnose primary immunodeficiency in which the body’s immune system does not function properly and has trouble fighting infections. In most patients, it is caused by mutations in the CXCR4 gene that result in white blood cells getting trapped in the bone marrow.
  • WHIM syndrome was named for its four main symptoms: Warts (related to infection with the Human Papilloma Virus (HPV)), Hypogammaglobulinemia (low immunoglobulin, or IG, levels), Infections (both bacterial and fungal), and Myelokathexis (a hyper-dense population of immune cells in the bone marrow). Approximately 30% to 40% of WHIM patients develop HPV-associated cancers as they age.
  • The incidence and prevalence of WHIM syndrome are not well established. Through market research, we estimate that there are more than 1,000 individuals with WHIM syndrome in the U.S. However, the diagnosis of WHIM is not well defined due to the emerging understanding of the genetics underlying WHIM syndrome, lack of universal or accessible genetic testing, and limited medical education and awareness of the disease, which is in part driven by the lack of available disease-modifying treatments.
  • To date, mavorixafor has demonstrated proof-of-concept in WHIM syndrome in a Phase 2 clinical trial, including clinically meaningful increases in neutrophil and lymphocyte biomarker counts, as well as a trend of reduction in infection rates and wart burden, and has been generally well tolerated. The FDA granted Breakthrough Therapy Designation (BTD) for mavorixafor in WHIM Syndrome based on the Phase 2 trial results.
  • Following positive results from the Phase 2 clinical trial, we initiated a global Phase 3 pivotal trial of mavorixafor in adults and pediatric patients (ages 12 and above) with WHIM.
  • The 4WHIM<link to whimtrial.com> Phase 3 clinical trial (NCT03995108<link to https://www.clinicaltrials.gov/ct2/show/NCT03995108?term=mavorixafor&draw=2&rank=2> is a global, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of mavorixafor in WHIM patients with mutations in the CXCR4 gene.
    • The primary endpoint of the 4WHIM trial is a clinically relevant reduction of severe neutropenia as measured by the increase in time above threshold (500 cells per microliter) for the absolute neutrophil count (or “TAT-ANC”) in peripheral blood.
    • Additional endpoints include assessments of other cell types in the blood, including absolute lymphocyte count, absolute monocyte count, and total white blood cells, and assessments of infection burden (severity, rate), as well as changes in cutaneous wart burden at 52 weeks. A number of quality-of-life measurements, health economic metrics, and other exploratory endpoints are also being assessed.
    • The trial is fully enrolled with patients aged 12 and older receiving mavorixafor or placebo orally once daily for 52 weeks; all patients then become eligible to receive treatment with mavorixafor in an open-label trial extension.
  • Results from the 4WHIM trial are expected in the fourth quarter of 2022.
  • There are no existing treatments that specifically target the underlying causes of WHIM syndrome; if approved, mavorixafor would be the first therapy available specifically to treat those diagnosed with WHIM syndrome.
 

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